Low therapeutic value of D‐penicillamine in a short‐term prospective trial in primary biliary cirrhosis

Abstract

A small double-blind controlled trial to evaluate the short-term effects of D-penicillamine therapy was carried out in 24 patients with primary biliary cirrhosis (PBC). The daily dose of D-penicillamine was increased monthly by 250 mg until a total of 1 g daily was reached. Two out of 11 patients (18%) were withdrawn because of side-effects, as also were 4 out of 13 (31%) patients receiving the placebo. Transient improvement in symptoms was observed in 4of 11 patients on D-penicillamine, but also in 5 of 13 patients from the placebo group. The proportion of patients showing a fall in serum IgM, IgG and hepatic copper was significantly larger for the D-penicillamine group than for the placebo group. No improvement in liver tests was observed, but the progression of inflammatory periportal liver cell destruction (piecemeal necrosis) was retarded in patients on D-penicillamine @=0.02). Data analysis within the Dpenicillamine group showed that lowering the dose of D-penicillamine to 500 mg daily abolished the effect on the serum immunoglobulins and hepatic copper. The beneficial effect of D-penicillamine therapy appears to be small and doserelated; side effects should not prevent its use, provided the drug is introduced slowly.

Systematic review and meta‐analysis: D‐Penicillamine vs. placebo/no intervention in patients with primary biliary cirrhosis – Cochrane Hepato‐Biliary Group

“…The trial publication with most completed data were regarded as the primary reference, from which data were extracted. Six trials compared d ‐penicillamine vs. placebo/no intervention 8, 9, 21–24 . Bodenheimer et al .…”

“…No trials reported sample size estimation. Five trials reported the number of dropouts in d ‐penicillamine (74 patients) and in control group (16 patients), respectively 9, 21–24 . Bodenheimer et al .…”

“…The major rationale for treating patients with primary biliary cirrhosis is its abilities to induce cupruresis, to inhibit lymphocytes, and to decrease circulating immune complexes 4–6 . There are conflicting reports concerning the effects of d ‐penicillamine for primary biliary cirrhosis 7–9 . According to a UK survey, 10 nearly 3% of the patients with primary biliary cirrhosis are being treated with d ‐penicillamine.…”

Potential of the international scoring system for the diagnosis of Wilson disease to differentiate Japanese patients who need anti‐copper treatment

“…Even though an ATP7B heterozygote could be affected by secondary copper toxicosis of primary biliary cirrhosis, the treatment of choice should be ursodeoxycholic acid rather than penicillamine. 29,30 In conclusion, although the number of patients studied was small, the internationally proposed system could be considered fairly reliable for screening Japanese patients with WD. Long-range PCR was recommended for screening because there were patients with gross deletions involving more than one exon in the ATP7B gene.…”

“…A carrier state of HCV in a heterozygous member of the WD family was successfully treated with anti‐HCV agents (case 14). Even though an ATP7B heterozygote could be affected by secondary copper toxicosis of primary biliary cirrhosis, the treatment of choice should be ursodeoxycholic acid rather than penicillamine 29,30 …”